Extensive Hepatectomy as an Alternative to Liver Transplant in Advanced Hepatoblastoma: A New Protocol Used in a Pediatric Liver Transplantation Center.

BACKGROUND: Surgery is a key factor in the treatment of hepatoblastoma, but choosing between an aggressive resection and liver transplant may be an extremely difficult task. The aim of this study was to describe the outcomes of patients with advanced hepatoblastoma: pretreatment extent of disease (PRETEXT)/post-treatment extent of disease (POST-TEXT) III and IV undergoing aggressive resections or living donor liver transplant in cases involving the entire liver. Based on this experience, a new protocol for the treatment of these patients was proposed. METHODS: A retrospective study included patients with advanced hepatoblastoma (POST-TEXT III and IV) who were referred for a liver transplant from 2010 to 2017. RESULTS: A total of 24 children were included: 13 (54.2%) were male, with a median age at diagnosis of 42 months (range, 15-120 months), and a history of prematurity was identified in 20.8% of the patients. Ten cases (41.7%) were staged as PRETEXT/POST-TEXT III, and 12 cases (50.0%) were staged as PRETEXT/POST-TEXT IV. Two patients were referred after posthepatectomy recurrence. Five patients underwent a liver transplant, with recurrence and death in 2 patients (40.0%) within a mean period of 6 months. In the extensive hepatectomy group, there was recurrence in 6 patients (31.6%), with disease-free outcomes and overall survival in 63.2% and 94.7% of patients, respectively. CONCLUSION: In cases of advanced hepatoblastoma, an extensive surgical approach is a valuable option. The fact that the team was fully prepared to proceed with living donor liver transplant allowed the surgeon to be more aggressive and to switch to transplantation when resection was not possible.

Liver regeneration model in growing rats with hepatic artery ligation: histologic and molecular studies.

BACKGROUND: Liver transplantation is an effective treatment for irreversible liver diseases. The incidence of hepatic artery thrombosis remains high. Our objective was to analyze the effect of ligature of the hepatic artery on liver regeneration in a growing animal model. METHODS: Seventy-five male Wistar rats were divided into the following 3 groups: group 1 (sham, G1): incision without intervention; group 2 (G2): 70% hepatectomy; group 3 (G3): 70% hepatectomy and ligation of the hepatic artery. Preceding the 70% hepatectomy, a hepatic artery ligature was performed with resection of a segment of the artery. The liver specimens were stained with hematoxylin-eosin, and immunohistochemical staining for Ki-67 was performed. The expression of the interleukin (IL) 6 gene was studied by means of reverse-transcription polymerase chain reaction. RESULTS: G2 and G3 demonstrated similar tendencies toward an increase in the gain weight ratio over time. The mitotic activity was significantly lower at 72 hours in G3 than in G2. There was no difference between Ki-67 staining between G2 and G3. The expression of the IL-6 gene was present in all of the groups, lower in G1, with no difference between G2 and G3. CONCLUSIONS: The experimental model was feasible and adequate for these investigations. Hepatectomy stimulated hepatocyte proliferation, and the obstruction of the arterial flow did not affect liver regeneration.

Living related donor liver transplantation in children.

OBJECTIVE: The objective of this study was to report our experience with pediatric orthotopic liver transplantation (OLT) with living related donors. METHODS: We performed a retrospective chart analysis of 121 living related donor liver transplantations (LRDLT) from June 1998 to June 2010. RESULTS: Indications were biliary atresia (BA; n = 81), primary sclerosing cholangitis (n = 5), α-1 antitrypsin deficiency (n = 4); cholestasis (n = 9), fulminant hepatic failure (n = 8), autoimmune hepatitis (n = 2), Alagille syndrome (n = 4), hepatoblastoma (n = 3), tyrosinemia (n = 2), and congenital hepatic fibrosis (n = 3). The age of the recipients ranged from 7-174 months (median, 22) and the weights ranged from 6-58 kg (median, 10). Forty-nine children (40.5%) weighed ≤10 kg. The grafts included the left lateral segment (n = 108), the left lobe (n = 12), and the right lobe (n = 1). The donors included 71 mothers, 45 fathers, 2 uncles, 1 grandmother, 1 grandfather, and 1 sister with a median age of 29 years (range, 16-53 ys) and a median weight of 68 kg (range, 47-106). Sixteen patients (12.9%) required retransplantation, most commonly due to hepatic artery thrombosis (HAT; n = 13; 10.7%). The other complications were biliary stenosis (n = 25; 20.6%), portal vein thrombosis (PVT; n = 11; 9.1%), portal vein stenosis (n = 5; 4.1%), hepatic vein stenosis (n = 6; 4.9%), and lymphoproliferative disorders (n = 8; 6.6%). The ultimate survival rate of recipients was 90.3% after 1 year and 75.8% after 3 years. Causes of early death within 1 month were HAT (n = 6), PVT (n = 2), severe graft dysfunction (n = 1), sepsis (n = 1), and intraoperative death in children with acute liver failure (n = 2). Causes of late deaths included lymphoproliferative disease (n = 3), chronic rejection (n = 2), biliary complications (n = 3), and recurrent disease (n = 3; hepatoblastoma and primary sclerosing cholangitis). CONCLUSIONS: Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio.

Hepatic artery graft in pediatric liver transplantation: single-center experience with 58 cases.

INTRODUCTION: The use of arterial grafts (AG) in pediatric orthotopic liver transplantation (OLT) is an alternative in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, and retransplantations (re-OLT) due to hepatic artery thrombosis (HAT). AG have been crucial to the success of the procedure among younger children. Herein we have reported our experience with AG. METHODS: We retrospectively reviewed data from June 1989 to June 2010 among OLT in which we used AG, analyzing indications, short-term complications, and long-term outcomes. RESULTS: Among 437 pediatric OLT, 58 children required an AG. A common iliac artery interposition graft was used in 57 cases and a donor carotid artery in 1 case. In 38 children the graft was used primarily, including 94% (36/38) in which it was due to poor hepatic arterial inflow. Ductopenia syndromes (n = 14), biliary atresia (BA; n = 11), and fulminant hepatitis (n = 8) were the main preoperative diagnoses among these children. Their mean weight was 18.4 kg and mean age was 68 months. At the mean follow-up of 27 months, multiple-organ failure and primary graft nonfunction (PNF) were the short-term causes of death in 9 children (26.5%). Among the remaining 29 patients, 2 (6,8%) developed early graft thrombosis requiring re-OLT; 5 (17%) developed biliary complications, and 1 (3.4%) had asymptomatic arterial stenosis. In 20 children, a graft was used during retransplantation. The main indication was HAT (75%). BA (n = 15), ductopenia syndromes (n = 2), and primary sclerosing cholangitis (n = 2) were the main diagnoses. Their mean weight was 16.7 kg and age was 65 months. At a mean follow-up of 53 months, 7 children died due to multiple-organ failure or PNF. Among the remaining 13 patients, 3 developed biliary complications and 1 had arterial stenosis. No thrombosis was observed. CONCLUSION: The data suggested that use of an AG is useful alternative in pediatric OLT. The technique is safe with a low risk of thrombosis.

Orthotopic liver transplantation in biliary atresia: a single-center experience.

INTRODUCTION: Biliary atresia (BA) is the leading indication for orthotopic liver transplantation (OLT) among children. However, there are technical difficulties, including the limited dimensions of anatomical structures, hypoplasia and/or thrombosis of the portal vein and previous portoenterostomy procedures. OBJECTIVE: The objective of this study was to present our experience of 239 children with BA who underwent OLT between September 1989 and June 2010 compared with OLT performed for other causes. METHODS: We performed a retrospective analysis of patient charts and analysis of complications and survival. RESULTS: BA was the most common indication for OLT (207/409; 50.6%). The median age of subjects was 26 months (range, 7-192). Their median weight was 11 kg (range, 5-63) with 110 children (53.1%) weighing ≤10 kg. We performed 126 transplantations from cadaveric donors (60.8%) and 81 from living-related donors (LRD) (39.2%). Retransplantation was required for 31 recipients (14.9%), primarily due to hepatic artery thrombosis (HAT; 64.5%). Other complications included the following: portal vein thrombosis (PVT; 13.0%), biliary stenosis and/or fistula (22.2%), bowel perforation (7.0%), and posttransplantation lymphoproliferative disorder (PTLD; 5.3%). Among the cases of OLT for other causes, the median age of recipients was 81 months (range, 11-17 years), which was higher than that for children with BA. Retransplantation was required in 3.5% of these patients (P < .05), mostly due to HAT. The incidences of PVT, bowel perforation, and PTLD were significantly lower (P < .05). There was no significant difference between biliary complications in the 2 groups. The overall survival rates at 1 versus 5 years were 79.7% versus 68.1% for BA, and 81.2% versus 75.7% for other causes, respectively. CONCLUSIONS: Children who undergo OLT for BA are younger than those engrafted for other causes, displaying a higher risk of complications and retransplantations.

Rex shunt for acute portal vein thrombosis after pediatric liver transplantation in children with biliary atresia.

BACKGROUND/PURPOSE: Posttransplantation portal vein thrombosis (PVT) can have severe health consequences, and portal hypertension and other consequences of the long-term privation of portal inflow to the graft may be hazardous, especially in young children. The Rex shunt has been used successfully to treat PVT patients since 1998. In 2007, we started to perform this surgery in patients with idiopathic PVT and late posttransplantation PVT. Herein we have reported our experience with this technique in acute posttransplantation PVT. METHODS: Three patients of ages 12, 15, and 18 months underwent cadaveric (n = 1) or living donor (n = 2) orthotopic liver transplantation (OLT). All patients had biliary atresia with portal vein hypoplasia; they developed acute PVT on the first postoperative day. They underwent a mesenteric-portal surgical shunt (Rex shunt) using a left internal jugular vein autograft (n = 2) or cadaveric iliac vein graft (n = 1) on the first postoperative day. RESULTS: The 8-month follow-up has confirmed shunt patency by postoperative Doppler ultrasound. There have been no biliary complications to date. CONCLUSIONS: The mesenteric-portal shunt (Rex shunt) using an autograft of the left internal jugular or a cadaveric vein graft should be considered for children with acute PVT after OLT. These children usually have small portal veins; reanastomosis is often unsuccessful. In addition, this technique has the advantage to avoid manipulation of the hepatic hilum and biliary anastomosis. Although this study was based on a limited experience, we concluded that this technique is feasible, with great benefits to and low risks for these patients.

Multiple clinical presentations of lymphoproliferative disorders in pediatric liver transplant recipients: a single-center experience.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naïve prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.

Sirolimus in pediatric liver transplantation: a single-center experience.

BACKGROUND AND AIMS: Liver transplantation (OLT) in children has seen significant improvements in recent years. Long-term immunosuppressive strategies have focused on avoiding the risks of long-term immunosuppression, particularly nephrotoxicity, de novo malignancy and late infections. Since its introduction in renal transplantation in 1999, sirolimus (SRL) has been used by an increasing number of liver transplant centers. The aim of this study was to review the experience using SRL in pediatric liver transplant recipients at a single center. METHODS: Between 1989 and 2006, 318 children underwent OLT including 13 who were converted to SRL therapy because of tacrolimus-related side effects. The indications were posttransplant lymphoproliferative disease (PTLD; n = 11), nephrotoxicity (n = 1), and de novo autoimmune hepatitis (n = 1). One patient with PTLD previously concurrently displayed chronic rejection. SRL dosages ranged between 0.4 and 5 mg/d. The median duration of follow-up was 18 months. RESULTS: PTLD recurred in 1 patient. There were no episodes of acute rejection. One child developed hyperlipidemia that resolved with diet and medication. CONCLUSIONS: Conversion from tacrolimus to SRL in selected pediatric liver transplant recipients is safe. Children with PTLD may benefit from immunosuppression with SRL after liver transplantation.

"Rex shunt" for the treatment of portal vein thrombosis after pediatric liver transplantation: a case report.

BACKGROUND AND PURPOSE: Late portal vein thrombosis (PVT) can be extremely well tolerated, although portal hypertension and other consequences of the long-term deprivation of portal inflow to the graft may be hazardous, especially in young children. Recently, the "Rex shunt" has been used successfully to treat these patients. We now report the initial experience with this novel technique. METHODS: A 3-year-old girl with PVT at 7 months after whole organ cadaveric liver transplant displayed portal hypertension with an episode of gastrointestinal bleeding, requiring a mesenteric-portal surgical shunt ("Rex shunt") using a left internal jugular vein autograft. RESULTS: Upon current follow-up of 6 months, postoperative Doppler ultrasound confirmed shunt patency. Endoscopic status was significantly improved after surgery with resolution of portal hypertension. There was no recurrence of bleeding. CONCLUSIONS: The mesenteric-portal shunt ("Rex shunt"), using a left internal jugular vein autograft, should be considered for children with late PVT after liver transplantation. Although this is an initial experience, we may conclude that this technique is feasible, with great potential benefits and low risks for these patients.

Pediatric liver transplantation: fourteen years of experience at the children institute in São Paulo, Brazil.

This study reports the 14-year experience of a single center on 206 liver transplantations from living and cadaveric donors performed in 179 pediatric patients. Biliary atresia (57.2%) and fulminant hepatitis (9.8%) were the most frequent indications. The mean age of the recipients was 3 years, 7 months (9 months to 18 years) and mean weight was 14 kg (7 to 57 kg). The allografts were distributed as 82 (39.8%) whole cadaveric, 76 (36.9%) reduced-size cadaveric, 46 (22.3%) living donor liver transplants, and 2 (0.9%) ex situ split livers. The waiting periods were 25 days for living donors and 2.5 years for cadaveric donors (P <.001). Twenty-seven children were retransplanted with hepatic artery thrombosis the most frequent indication. The postoperative complications were: primary nonfunction (12.2%), biliary stenosis (28.8%), hepatic artery thrombosis (12.2%), portal vein stenosis (4.9%), hepatic vein stenosis (6.9%), and lymphoproliferative disorder (5.9%). The diagnosis of biliary stenosis was obtained by liver biopsy and transhepatic cholangiography and treated by balloon dilatation, although four children (3.9%) required a redo hepaticojejunostomy. The venous stenoses were percutaneously dilated with five-children (4.9%) requiring venous stents. The incidence of hepatic vein stenosis was 15.6% among living donor and 2.5% in cadaveric liver transplantation (P <.05). The overall 5-year patient and graft survivals were 70.2% and 65.1%. Liver transplantation provides excellent long-term survival. The use of grafts from living donors decreases the waiting periods but increases the incidence of hepatic vein stenosis.

Basiliximab-chimeric anti-IL2-R monoclonal antibody in pediatric liver transplantation: comparative study.

Basiliximab is a monoclonal antibody that binds to the alpha subunit (CD(25)) of the interleukin-2 receptor of activated T lymphocytes. The advantage of basiliximab in organ transplantation is the reduce possibility to calcineurin inhibitor dosages to avoid nephrotoxicity. Basiliximab has significantly reduced the incidence of acute rejection (AR) in renal transplant recipients; however, the results are uncertain in liver transplantation (LT). The objective of this investigation was to assess the effect of basiliximab to prevent AR in the first 6 months after pediatric LT. From March 2000 to October 2001, 32 recipients of a primary orthotopic cadaveric or living donor LT were given basiliximab by intravenous bolus injection on the day of transplantation (day 0) and on day 4. Four children who received one dose were excluded from the study. The rate and the intensity of AR episodes, the incidence of chronic rejection, serum creatinine level, incidence of infections, adverse side effects, and daily oral dosage of cyclosporine (Neoral) to maintain the target blood level of 850 to 1000 mg/dL at C2, 2 hours after the administration, were analyzed in the remaining 28 recipients. Results were compared to those obtained from a matched historical group (n = 28) of similar age, weight, and hepatic diseases distribution. None of the analyzed parameters was statistically significant (P >.05) except for the daily oral dose of cyclosporine (7 to 13 mg/kg/dose, P <.05). In our series, the addition of basiliximab to the immunosuppressive therapy did not reduce the incidence of AR in pediatric LT.